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Adalimumab for Treatment of Noninfectious Uveitis

Immunogenicity and Clinical Relevance of Measuring Serum Drug Levels and Antidrug Antibodies
Published:September 27, 2016DOI:https://doi.org/10.1016/j.ophtha.2016.08.025

      Purpose

      To evaluate the rate of immunogenicity induced by adalimumab and its relationship with drug serum levels and clinical responses in patients with noninfectious uveitis.

      Design

      Prospective observational study.

      Participants

      Consecutive patients from 1 referral center who initiated treatment with adalimumab for active noninfectious uveitis resistant to conventional therapy.

      Methods

      All patients received 40 mg adalimumab every other week. Patients were evaluated clinically and immunologically before and after 4, 8, and 24 weeks of treatment.

      Main Outcome Measures

      Clinical evaluation included assessment of changes in visual acuity, degree of inflammation in the anterior chamber and vitreous cavity, central macular thickness, and retinal angiographic leakage. Immunologic evaluation included assessment of serum trough adalimumab and antibodies against adalimumab (AAA) levels and class II HLA typing.

      Results

      Twenty-five patients were enrolled. Overall, 18 of 25 patients (72%) showed a favorable clinical response to adalimumab therapy. Eleven patients (44%) achieved a complete response and 7 (28%) achieved a partial response. However, 7 of 25 patients (28%) were considered nonresponders. Median trough adalimumab serum levels were higher in responders than in nonresponders (P < 0.001). We observed AAA positivity (AAA+) at least 1 time point in 8 of 25 patients (32%), including 4 with transitory AAA and 4 with permanent AAA. In all patients with permanent AAA+, trough adalimumab levels became undetectable (P < 0.001). However, in patients who demonstrated transitory AAA+, no correlation was observed between AAA titers and adalimumab trough levels (P = 0.2).Concomitant immunosuppression did not show any protective effect on adalimumab immunogenicity in our cohort. An association between the presence of AAA+ and a worse uveitis outcome was observed only in patients with permanent AAA+, which correlated with undetectable adalimumab trough levels (P = 0.014).

      Conclusions

      Treatment of noninfectious uveitis with adalimumab is associated with high rates of favorable clinical response. Overall, adalimumab trough levels were higher in responder patients. Development of permanent AAA was associated with undetectable trough adalimumab levels and worse uveitis outcome. Immunogenicity was more common in patients in whom uveitis was associated with a systemic disease and was not influenced by concomitant immunosuppressors.

      Abbreviations and Acronyms:

      AAA (antibody against adalimumab), AAA+ (antibody against adalimumab positivity), FA (fluorescein angiography), HLA (human leukocyte antigen), OCT (optical coherence tomography), TNF (tumor necrosis factor)
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